Degenerin/ epithelial sodium channels (Deg/ENaC) are voltage-insensitive cationic channels that are widely expressed in epithelial and neuronal tissues. In mammals, several Deg/ENaC subunits are critical for maintaining sodium ionic gradient across epithelial barriers in different tissues. Several members of the family are also highly expressed in sensory neurons of various modalities. Yet, the physiological role of Deg/ENaC channels at the sensory level is still poorly defined. Heterologous expression studies suggest that Deg/ENaC channels can be activated by a variety of extracellular stimuli such as protons, peptides, proteases, and mechanical stretch. The Deg/ENaC family is exceptionally large in the genomes of Drosophila species;while only eight members of the family have been identified in mammals, the fly genome contains thirty independent Deg/ENaC genes. These data suggest that members of the Deg/ENaC family in the fruit fly are highly specialized. The Deg/ENaC subunit abundance in the fly genome presents an opportunity to use the power of Drosophila genetics to elucidate the sensory roles of specific Deg/ENaC ion channels, and hence gain new knowledge about the physiological roles of Deg/ENaC ion chanels in the peripheral nervous systm. This proposal is focused on characterizing one Deg/ENaC family member, aguesic (agu), which was identified as a channel highly enriched in gustatory-like neurons in the fly. Preliminary data suggest that agu has a role in courtship related behaviors. Aim 1 will test the hypotheses that agu-expressing cells are sex-specific and functionally distinct from the feeding related gustatory sensory system. Aim 2 will test the hypothesis that AGU functions as a chemoreceptor. Aim 3 will test the hypothesis that other agu-like Deg/ENaC subunits have chemosensory roles. Strategy will include development of genetic and transgenic tools, physiological measures of neuronal activation, and ectopic activation of sensory neurons to unravel the sensory roles of chemosensory-specific Deg/ENaC channels in Drosophila. Understanding the sensory physiological role for Deg/ENaC ion channels in the fruit fly model could reveal novel functions for these channels in a wide range of mammalian sensory modalities such as taste, pain, and nociception. PUBLIC HEALTH RELEVANCE: Animals use functionally diverse array of proteins to constantly extract information about their environment. This project examines the role of specific degenrin/ epithelial sodium channels and the sensory neurons expressing them in mediating chemosensory signals associated with social interactions.